In this renewal application we are requesting funds for eleven projects. Four of these are continuations of currently funded projects (Ruddle; Pawelek; Ward; Weissman); seven are new (Eisenstadt; Garen; Adelberg; Breakefield; Murphy; Seashore; Mahoney). As was true with our earlier application, the methodologic thread which runs through the majority of these projects involves study of cultured mammalian cells. Seven of the eleven projects employ this general system. Although the specific questions asked and the cell type employed vary considerably, some common themes emerge. For instance, Ruddle and Eisenstadt will attempt to assign specific gene functions to specific chromosomes by transferring genes or chromosomes from one cell to another. Ward, too, will transfer genetic material from cell to cell, but in his work the genes transferred will be the entire parvovirus particle whose replication pattern he hopes to define. Adelberg, Breakefield and Pawelek will use chemical mutagens to select for cells expressing functions of interest to them. Questions concerning development and differentiation are echoed in several proposals: Garen hopes to use immunochemical methods to identify nuclear proteins concerned with differentiation; Pawelek will characterize further the biochemistry and genetics of that highly differentiated function, pigmentation; Breakefield will explore the degree to which cultured fibroblasts express the genes concerned with neurotransmitter metabolism. The investigators initiating these projects recognize the common methods and rationale of their work; they and the director are committed to both communication and collaboration via informal luncheons, discussions, and workshops concerned with the genetics of somatic cells.